Recordati B V — Sylvant EMA EPAR public assessment report (EMEA/H/C/003708, 2014)
Recordati B V · 2014 · EMA EPAR public assessment report · company profile →
Report summary
The CHMP granted a positive opinion for Sylvant (siltuximab) on March 20, 2014, for HIV-negative and HHV-8-negative adult patients with multicentric Castleman's disease (MCD). Siltuximab, an orphan medicinal product, targets IL-6. Manufacturing, quality control, and non-clinical studies, including toxicology and pharmacokinetics, supported its development. Non-clinical studies in monkeys showed no reproductive toxicity. Human pharmacokinetics revealed dose-proportionality and a 17.73-20.64 day half-life, achieving steady-state by the sixth infusion at 11 mg/kg every 3 weeks, leading to sustained CRP suppression. Clinical trials demonstrated significant efficacy, with a 34.0% durable tumor and symptomatic response rate for siltuximab versus 0% for placebo. While some adverse events like infections were more common, severe events were low. Safety concerns include malignancy, infusion reactions, and hepatotoxicity, with routine risk minimization measures in place. Long-term safety data are limited, and a registry is planned for further monitoring.
Key findings — cited to the page
| Subjects with AEs of toxicity grade 3 or higher | 54.1 % | C0328T03 · p.38 |
| Anemia (Grade 3 or higher AE, placebo group) | 12 % | · p.65 |
| Subjects with Grade 3 or higher AEs (placebo group) | 54 % | CNTO328MCD2001 · p.65 |
| Skin and Subcutaneous Tissue Disorders (Grade 3 or higher AEs, siltuximab group) | 11 % | · p.65 |
| Infections and Infestations (Grade 3 or higher AEs, placebo group) | 15 % | · p.65 |
| Gastrointestinal disorders (Grade 3 or higher AEs, placebo group) | 12 % | · p.65 |
| Blood and Lymphatic System Disorders (Grade 3 or higher AEs, placebo group) | 19 % | · p.65 |
| Subjects with Grade 3 or higher AEs (siltuximab group) | 47 % | CNTO328MCD2001 · p.65 |
| Metabolism and Nutrition Disorders (Grade 3 or higher AEs, siltuximab group) | 17 % | · p.65 |
| General Disorders and Administration Site Conditions (Grade 3 or higher AEs, siltuximab group) | 15 % | · p.65 |
| IC50 for inhibition of SAA production by HepG2 cells | 34.43 ng/ml | · p.19 |
| Incidence of infections and infestations of any grade (placebo) | 35 % | · p.66 |
Source: Recordati B V ↗ · License: EMA - reuse permitted with acknowledgement. Summary and findings are extracted from the published document; every figure cites its page. Informational only — not investment advice. Explore the Immunology library →